Scientific Reports
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2026
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IF 4.9
Wang Ying,Zhang Qi,Liu Jiahui,Kuang Hongying,Feng Xiaoling
Polycystic ovary syndrome (PCOS) is the most prevalent endocrine disorder among women of childbearing age and the leading cause of anovulatory infertility worldwide, with the death of granulosa cells implicated in its pathogenesis. However, the mechanisms underlying granulosa cell death remain unclear. Limited research has explored the association between GATA binding factor 1 (GATA1) and adverse pregnancy outcomes, yet its role in PCOS is still elusive. This study established an in vivo PCOS model via dehydroepiandrosterone administration in mice and used ovarian-like KGN cells to explore granulosa cell function. Results showed elevated ovarian GATA1 expression in PCOS mice. Functionally, GATA1 overexpression in KGN cells increased lipid reactive oxygen species, malondialdehyde, and iron, while reducing glutathione. Notably, all these effects of GATA1 were mitigated by a ferroptosis inhibitor Ferrostatin-1. Furthermore, GATA1 knockdown alleviated lipid peroxidation and iron overload in KGN cells induced by a ferroptosis inducer Erastin. Mechanistically, GATA1 directly bound the transferrin receptor (TFRC) promoter to enhance its transcription. Additionally, TFRC overexpression counteracted GATA1 knockdown’s protective effects against Erastin-induced ferroptosis. Collectively, GATA1 promotes granulosa cell ferroptosis via TFRC transcriptional activation, contributing to PCOS pathogenesis. GATA1 regulatory pathways may serve as potential therapeutic targets for PCOS.
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ANALYTICA CHIMICA ACTA
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2026
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IF 6.1
Xiping Cui,Qiyi He,Huiyi Yang,Mingxia Lin,Suqing Zhao,Yunping Mu
Background Measurement of cortisol levels is still a complex multi-step process in immunoassay. The isolation of single-chain variable fragment (scFv) from phage-display library is an effective approach to generate antibody-enzyme fusion protein, which can be used to improve the performance of immunoassay. Results In this work, the specific scFv against cortisol was isolated from native chicken-derived phage display library by the stringent bio-panning strategy. The obtained scFv was further fused with nanoluciferase (Nluc), named scFv-Nluc. Compared with scFv-based enzyme-linked immunosorbent assay (ELISA), the bioluminescent enzyme immunoassay (BLEIA) based on scFv-Nluc was conducted in one-step strategy, which could reduce the assay time. The half maximal inhibitory concentration (IC 50 ) of the one-step BLEIA was calculated to be 203 ng/mL, which was 5-fold lower than the scFv-based ELISA (IC 50 of 1139 ng/mL). When the BLEIA and ELISA are applied to serum samples subjected to 200-fold dilution, the corresponding original-serum equivalent IC 50 values are 41 μg/mL for BLEIA and 228 μg/mL for ELISA, respectively. The established BLEIA exhibited excellent selectivity for cortisol among the analogues, while the satisfactory recoveries between 85.1 % and 120.1 % were obtained. Significance The results above demonstrated that both scFv and scFv-Nluc could be utilized as useful reagents for immunoassay, but the scFv-Nluc-based BLEIA could further enhance the performance of immunoassay, which may represent the promising method for cortisol analysis.
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Journal of Ovarian Research
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2026
·Vol. 19
·期 1
·52
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IF 4.2
Ying Zhu,Hongqiu Zhu,Junjie Li,Peijuan Wu,qian Zhang,Mengxue Duan,Yan Li
Objectives The current treatments of polycystic ovarian syndrome (PCOS) have limited selectivity and effectiveness. Zishen Yutai Wan (ZSYTW) has shown therapeutic effects on patients with PCOS. This study aims to discover potential therapeutic targets and molecular mechanisms based on network pharmacology and molecular docking. Methods A disease gene set related to PCOS was collected from three public databases, a ZSYTW target gene set was established using the Traditional Chinese Medicine Systems Pharmacology database and Traditional Chinese Medicine and Chemical Components Database, and an intersection of two gene sets to obtain intersecting genes. Protein-protein interaction (PPI) network were performed on intersecting genes. Molecular docking further confirmed the high affinity and stability between the active compounds of ZSYTW and core targets. Finally, PCOS model mice were used to verify the results. Results Network pharmacology showed that AKT1 , TNF , IL6 , TP53 , and ESR1 were the key targets of ZSYTW against PCOS. Molecular docking demonstrated beta-sitosterol and stigmasterol exhibit strong binding affinities and binding stability with core targets, and p53 has the highest affinity with core components of ZSYTW. Mice experiment showed that compared with the control group, the expression of p53 protein and total apoptosis rate of ovarian granulosa cells in PCOS group were significantly increased ( P < 0.001). And ZSYTW could decrease the increased expression of P53 protein and total apoptosis rate of granulosa cells ( P < 0.001). Conclusion ZSYTW could effectively improve PCOS by regulating p53 and apoptosis of ovarian granulosa cells.
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Frontiers in Pharmacology
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2026
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IF 4.8
Yanping Wang,Xianmei Jiang,Shuyi Wu,Qiaohui Wang,Dan Zuo,Biao Huang,Li Jian,Yu Yang,Yong Cai,Xingjian Wen,Ling Yao,Shan Geng
Introduction: Intestinal dysbiosis, characterized by reduced diversity and enrichment of pro-inflammatory taxa, is implicated in the pathogenesis of polycystic ovary syndrome (PCOS). Ramulus mori (Sangzhi) alkaloids (SZ-A), approved in China for type 2 diabetes with broad metabolic effects, remain untested as a microbiota-targeted intervention for PCOS.Methods: In a dehydroepiandrosterone (DHEA)-induced rat model of PCOS, we evaluated the therapeutic efficacy of SZ-A and its underlying microbiota–metabolite interactions through integrated assessments of reproductive and endocrine–metabolic function, oxidative stress, inflammatory cytokines, and gut microbiota and serum metabolite profiles.Results: Relative to SD rats, PCOS rats showed approximately 10-fold higher cystic follicle burden and a one-third reduction in corpora lutea, with serum testosterone rising from 0.12 ± 0.08 to 0.27 ± 0.08 ng/mL, total bile acids falling from 34.22 ± 5.52 to 20.63 ± 4.94 μM, and HOMA-IR significantly increased (all p < 0.05). SZ-A treatment reduced cystic follicles, restored estrous cyclicity and luteal formation, and shifted testosterone, total bile acids, and HOMA-IR toward SD levels. At the molecular level, SZ-A appears to act by remodeling gut microbiota composition and serum metabolite profiles. SZ-A significantly shifted microbial β-diversity in PCOS rats while retaining a community dominated by Bacteroidetes and Firmicutes with Lactobacillus and Treponema_2 as key genera. Untargeted metabolomics identified 13 PCOS-associated serum metabolites that were significantly reduced after SZ-A treatment (p < 0.05), highlighting fenoldopam as a putative mediator of its beneficial effects on ovarian function and metabolic homeostasis. With respect to oxidative injury, serum malondialdehyde (MDA) levels in PCOS rats were approximately twice those of the SD group, while total antioxidant capacity (T-AOC) and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were significantly reduced (p < 0.05); treatment with SZ-A markedly attenuated these alterations (p < 0.05). Besides, it suppressed systemic inflammation by reducing interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) levels in serum and relevant tissues (p < 0.05).Discussion: Collectively, these findings indicate that SZ-A alleviates PCOS by attenuating intestinal oxidative stress and normalizing gut microbiota–metabolite interactions, and highlight fenoldopam as a potential effector, supporting SZ-A as a promising therapeutic candidate for PCOS.
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ACS Synthetic Biology
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2023
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IF 4.7
Ruosi Zhang,Mingdong Yao,Haidi Ma,Wenhai Xiao,Ying Wang,Yingjin Yuan
Substrate competition within a metabolic network constitutes a common challenge in microbial biosynthesis system engineering, especially if indispensable enzymes can produce multiple intermediates from a single substrate. Androstenedione (4AD) is a central intermediate in the production of a series of steroidal pharmaceuticals; however, its yield via the coexpression of 3β-hydroxysteroid dehydrogenase (3β-HSD) and 17α-hydroxylase/17,20-lyase (CYP17A1) in a microbial chassis affords a nonlinear pathway in which these enzymes compete for substrates and produce structurally similar unwanted intermediates, thereby reducing 4AD yields. To avoid substrate competition, we split the competing 3β-HSD and CYP17A1 pathway components into two separate Yarrowia lipolytica strains to linearize the pathway. This spatial segregation increased substrate availability for 3β-HSD in the upstream strain, consequently decreasing the accumulation of the unwanted intermediate 17-hydroxypregnenolone (17OHP5) from 94.8 ± 4.4% in single-chassis monocultures to 24.8 ± 12.6% in cocultures of strains expressing 3β-HSD and CYP17A1 separately. Orthologue screening to increase CYP17A1 catalytic efficiency and the preferential production of desired intermediates increased the biotransformation capacity in the downstream pathway, further decreasing 17OHP5 accumulation to 3.9%. Furthermore, nitrogen limitation induced early 4AD accumulation (final titer, 7.71 mg/L). This study provides a framework for reducing intrapathway competition between essential enzymes during natural product biosynthesis as well as a proof-of-concept platform for linear steroid production.
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TISSUE & CELL
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2023
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IF 2.6
Jing Cong,Mubai Li,Yu Wang,Hongli Ma,Xinming Yang,Jingshu Gao,Long Wang,Xiaoke Wu
Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder affecting women at reproductive age. The therapeutic effect of electroacupuncture (EA) on PCOS has been revealed, while the anti-PCOS mechanisms of EA have not been fully explored. In this study, PCOS were induced in rats by daily injection with dehydroepiandrosterone (DHEA) for 20 days and EA treatment was performed for 5 weeks. The mRNA expression profiles in ovarian tissues from control, PCOS, and EA-treated rats were examined by high-throughput mRNA sequencing. 5'-aminolevulinate synthase 2 (Alas2), a vital rate-limiting enzyme of the heme synthesis pathway, was selected to be further studied. PCOS led to the upregulation of Alas2 mRNA, whereas EA treatment restored this change. In vitro, primary ovarian granulosa cells (GCs) were challenged with H 2 O 2 to mimic the oxidative stress (OS) state in PCOS. H 2 O 2 induced apoptosis, OS, mitochondrial dysfunction, as well as Alas2 overexpression in GCs, while lentivirus-mediated Alas2 knockdown evidently restrained the above impairments. In summary, this study highlights the crucial role of Alas2 in cell apoptosis, OS, and mitochondrial dysfunction of PCOS GCs and provides potential therapeutic candidates for further investigation on PCOS treatment.
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MOLECULAR AND CELLULAR ENDOCRINOLOGY
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2022
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IF 4.369
Ying Wang,Jiyu Yang,Yu Wang,Yao Chen,Yiran Wang,Hongying Kuang,Xiaoling Feng
Polycystic ovary syndrome (PCOS) is a complex endocrine disease . Thioredoxin-interacting protein (TXNIP) promotes oxidative stress and triggers inflammation. Herein, we investigated the role and potential mechanism of TXNIP in PCOS. In a mouse model of dehydroepiandrosterone (DHEA)-induced PCOS, we found that TXNIP was upregulated in the ovaries , especially in granulosa cells (GCs). TXNIP was also upregulated in testosterone (T)-treated GCs in vitro. Knockdown of TXNIP by lentivirus-constructed shRNA attenuated T-induced GC injury and oxidative stress, as well as inflammation and the NLRP3 inflammasome . The mechanism by which TXNIP promotes inflammation may involve TXNIP dissociation from the TXNIP-TRX complex and binding to NLRP3 to form the inflammasome. Additionally, we verified that knockdown of TXNIP ameliorated ovarian injury and inflammation in mice with DHEA-induced PCOS in vivo. Collectively, we demonstrated that TXNIP is involved in GC inflammation by promoting NLRP3 inflammasome activation in PCOS.
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INTERNATIONAL IMMUNOPHARMACOLOGY
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2023
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IF 5.6
Lifeng Ding,Lili Jiang,Ze Xing,Huixu Dai,Jingzan Wei
The regulatory mechanism on granulosa cells (GCs) oxidative injury is becoming increasingly important in polycystic ovary syndrome (PCOS) studies. Serine/threonine kinase mitogen-activated protein 4 kinase 4 (Map4k4) is linked with oxidative injury and possibly associated with premature ovarian failure and ovarian dysgenesis. Herein, we investigated the function and mechanism of Map4k4 in a PCOS rat model. A microarray from GEO database identified Map4k4 was up-regulated in the ovarian of PCOS rats, and functional enrichments suggested that oxidative stress-associated changes are involved. We verified the raised Map4k4 expression in an established PCOS rat model and also in the isolated PCOS-GCs, which were consistent with the microarray data. Map4k4 knockdown in vivo contributed to regular estrous cycle, restrained steroid concentrations and ovarian injury in PCOS rats. Both Map4k4 silencing in vivo and in vitro attenuated the PCOS-related GC oxidative stress and apoptosis. Mechanically, Map4k4 activated the JNK/c-JUN signaling pathway. Importantly, a JNK agonist restored the suppressive effects of Map4k4 silencing on PCOS-induced granulosa cell injury and oxidative stress. Besides, Map4k4 may be a target gene of miR-185-5p. In conclusion, Map4k4, a potential target of miR-185-5p, is up-regulated and induces ovarian GC oxidative injury by activating JNK/c-JUN pathway in PCOS. The Map4k4/JNK/c-JUN mechanism may provide a new idea on the treatment of PCOS.
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Journal of Pharmaceutical Analysis
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2023
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IF 8.8
Tingting Yang,Jiayu Yuan,Yuting Peng,Jiale Pang,Zhen Qiu,Shangxiu Chen,Yuhan Huang,Zhenzhou Jiang,Yilin Fan,Junjie Liu,Tao Wang,Xueyan Zhou,Sitong Qian,Jinfang Song,Yi Xu,Qian Lu,Xiaoxing Yin
The occurrence of benign prostate hyperplasia (BPH) was related to disrupted sex steroid hormones, and metformin (Met) had a clinical response to sex steroid hormone-related gynaecological disease. However, whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear. Here, our clinical study showed that along with prostatic epithelial cell (PEC) proliferation, sex steroid hormones were dysregulated in the serum and prostate of BPH patients. As the major contributor to dysregulated sex steroid hormones, elevated DHT had a significant positive relationship with the clinical characteristics of BPH patients. Activation of AMPK by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor (AR)-mediated YAP1-TEAD4 heterodimers. Met’s anti-proliferative effects were blocked by AMPK inhibitor or YAP1 overexpression in DHT-cultured BPH-1 cells. Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.
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FOLIA HISTOCHEMICA ET CYTOBIOLOGICA
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2022
·Vol. 60
·期 3
·260-270
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IF 1.49
Ying Wang Yu Wang Yao Chen Qianqian Gao Lihui Hou Xiaoling Feng
Introduction. Abnormal ovarian angiogenesis is a common feature of polycystic ovary syndrome (PCOS), a typical endocrine disorder affecting women of reproductive age. Histone deacetylase 5 (HDAC5) has been documented as a suppressor of angiogenesis. The aim of this study was to explore the effect of HDAC5 on ovarian angiogenesis in a PCOS mouse model. Material and methods. PCOS was induced in female C57BL/6 mice by 20-day administration of dehydroepiandrosterone (DHEA). HDAC5 was over-expressed in PCOS mice by corresponding adenovirus injection. In total, 120 mice were used in this study. Western-blotting, real-time PCR, hematoxylin and eosin staining, enzyme-linked immunosorbent assay (ELISA), immunohistochemical staining, flow cytometry, and co-immunoprecipitation were respectively used to evaluate the effect of HDAC5 on PCOS mice. Results. PCOS ovaries showed a compensatory increase in HDAC5 expression, while HDAC5 over-expression alleviated abnormalities in ovarian morphology and serum hormone levels after PCOS modeling. HDAC5 inhibited ovarian angiogenesis in PCOS mice by regulating angiogenesis-related factors, such as VEGFA, platelet-derived growth factors B and D (PDGFB/D), and angiopoietins 1 and 2 (ANGPT1/2) and CD31. HDAC5 over-expression decreased levels of reactive oxygen species (ROS) and malondialdehyde, while promoting activities of catalase and superoxide dismutase in ovaries of PCOS mice, suggesting its suppressive effects on oxidative stress, an inducer of uncontrolled angiogenesis. Moreover, HDAC5 suppressed activation of angiogenesis-related HIF-1α/VEGFA/VEGFR2 signaling in PCOS ovaries partly via inhibiting VEGFR2 acetylation. Conclusions. This study reveals the protective role of HDAC5 in PCOS by inhibiting ovarian angiogenesis and provides a molecular candidate for PCOS therapy in the future.
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CHEMISTRY & BIODIVERSITY
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2022
·Vol. 19
·期 10
·e202200648
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IF 2.745
Xiao-San Li,Mao-Xun Yang,Yu-Hao Luo,He-Hui Zhan,Mei-Fang Chen,Yong-Mei Huang,Li Liu,Xue-Mei Yang
A series of novel D-ring fused or substituted steroidal N-heterocycles were synthesized, and their chemical structures were characterized by spectroscopic analysis. The anticancer activity of these compounds against four human cancer cell lines (MCF-7, H1299, HeLa and HepG2) were evaluated and the structure-activity relationship (SAR) was also investigated. Compound 3c displayed significant inhibitory activity on the four cancer cells with IC 50 values ranging from 3.88 to 10.05 μM. Overall, these studies indicated that construction of N-heterocyclic system with D-ring substituted containing a double bond at C-16 and C-17 or D-ring fused with [17,16-d]azolo[1,5-a]pyrimidine could be a promising strategy to improve antitumor activity for steroids deserved further investigation. Graphical
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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2022
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IF 3.322
Jing Cong,Yuehui Zhang,Xinming Yang,Yu Wang,Hui He,Mengying Wang
Polycystic ovary syndrome (PCOS) is a complicated endocrinopathy affecting women at reproductive age. Increasing evidence has shown the anti-PCOS effect of electroacupuncture (EA), a modified approach of traditional Chinese medical therapy “acupuncture”. However, the underlying mechanism of EA-alleviated PCOS waits further explored. In this study, experimental PCOS were induced in rats by dehydroepiandrosterone (DHEA) injection. Testosterone (T)-induced human ovarian granulosa cell (GC) line KGN was used to mimic PCOS in vitro . EA significantly alleviated histological changes and hormone disruption in PCOS rats. Besides, EA inhibited cell apoptosis, autophagy and the activation of endoplasmic reticulum (ER) stress-related PERK/eIF2α/ATF4/CHOP signaling in ovaries of PCOS rats. More interestingly, intermedin (IMD), a member of calcitonin gene-related peptide (CGRP), was evidently up-regulated in ovarian GCs after EA treatment, and its main bioactive form IMD 1-53 suppressed cell apoptosis, autophagy and PERK/eIF2α/ATF4/CHOP signaling in T-induced KGN cells. Consistent with IMD 1-53 , ER stress inhibitor 4-PBA exerted an inhibitory effect on T-induced cell apoptosis and autophagy in KGN cells. Collectively, this study validates the protective effect of EA on DHEA-induced PCOS, and proposes that IMD relieved apoptosis and autophagy in T-induced granulosa cells via inhibiting ER stress.
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